Neural cell transplants hold promise for the treatment of some neurodegenerative disorders, however, a fundamental question remains on the optimal cell type for this approach. Recently, we have developed and used monoclonal antibodies (mAbs) directed toward surface markers on human neural cells to identify and purify neural stem cells (NSCs) by fluorescence activated cell sorting. Sorted populations of NSCs were isolated and expanded using our long-term human neural cell culture system. Expanded cells and freshly isolated NSCs show the same ability to produce neurons and glia. This grant addresses directly a comparison of the in vivo reconstitution potential of lineage-committed progenitors versus stem cells or mature neurons. Our objectives are l) to identify, isolate, and characterize human CNS neuronal progenitors committed to the different lineages (e.g. dopaminergic, GABAergic) and test their proliferative and differentiation potential in vitro 2) to compare their in vivo reconstitution potential to neural stem cells or mature neurons. We propose to employ the same technology, used for NSCs, for the identification and isolation of lineage committed neuronal progenitor cells. Each cell population will be compared for their ability to engraft, survive, migrate, differentiate and contribute to biological function following transplantation. PROPOSED COMMERCIAL APPLICATIONS: A source of highly defined engraftable human cells capable of extensive neuronal regeneration could be an effective therapeutic product for the treatment of neurodegenerative disorders. A defined reproducible method for the identification, enrichment, and expansion of either human NSCs or committed progenitors would be a potential cell based therapy product available to a broader patient base than current fetal nigral transplants as a treatment for Parkinson's or Huntington's disease.